The long term objective of this project is to define the precise metabolic regulation of protein buildup and destruction in the living subject. Nutrition comprises multiple behavioral, physiological, and biochemical processes. The problem is important because of the major role of abnormal protein buildup or breakdown in multiple pathologic conditions. Two of these conditions, diabetes mellitus and malnutrition, are major public health problems worldwide. The specific goals of this proposal are to 1) mathematically define the effects of different plasma amine acid and leucine levels on protein metabolism in vivo and 2) develop a nonsteady state approach to protein turnover in vivo. The approach includes 1) use of the new technology of rapid analysis of plasma amino acids to prospectively define and maintain amino acid levels, simultaneous with the well established method of clamping hormone and glucose levels, 2) simultaneous measurement of the specific activities of multiply-labelled amino acids, and 3) design of experiments so that data can be analyzed by either a stochastic or general compartmental approach. The compartmental model can then be applied to the changes in protein turnover during acute changes in plasma hormone and amino acid levels.